Red Blood cells show increased caspase-3/7 activity in COVID-19 disease which is suppressed by a pan-caspase inhibitor
Recent reports suggest abnormalities in the RBCs in patients with COVID-19 (36-38). In the process of Ficoll separation, we observed a layer of RBCs contaminating the PBMC layer that was universally present in all samples from COVID-19 individuals (Figure 5A ). This finding was also present in up to 80% of COVID-19 convalescent subjects. Plasma from acutely infected COVID-19 subjects induced a similar finding when incubated overnight with plasma depleted whole blood of healthy patients. Treatment of the plasma samples with trypsin, DNAse, or heat inactivation did not abolish this effect (data not shown), suggesting a cell intrinsic process rather than due to cell surface changes. Cellular caspases are not limited to immune cells. RBCs do not express caspase-1, but have been shown to have detectable caspase-3 that increases with various disorders (36). We found that RBCs from acute COVID-19 subjects showed up-regulation of caspase-3/7 activity compared to healthy controls (Figure 5B ). Plasma from these patients also upregulated caspase-3 in healthy subjects’ RBCs. When healthy subjects’ RBCs were incubated with plasma from influenza infected patients this effect was not observed, although a similar RBC contamination was observed in these samples after Ficoll separation. Furthermore, EMR suppressed the caspase-3 up-regulation in samples incubated with COVID-19 patient-derived plasma, but did not change the baseline expression levels in influenza-plasma incubated samples.